Real world clinical characteristics of post-ET and post-PV MF

Patients diagnosed with essential thrombocythemia (ET) or polycythemia vera (PV) are at risk of progression to secondary myelofibrosis (MF).¹ Depending on initial diagnosis, subsequent disease is either classified as post-ET MF or post-PV MF; however, clinical features remain similar to those of primary MF.¹ Currently, there are very few prospective studies investigating patients with either post-ET or post-PV MF, and a prognostic model for primary MF may aid in the differentiation of secondary disease.¹

Shide et al.¹ performed a nationwide, longitudinal, prospective survey in Japan to clarify clinical characteristics associated with patients diagnosed with post-ET and post-PV MF. Here, we summarize the key results.

Methods

• Patients diagnosed with post-ET and post-PV MF between January 2012 and December 2021 were included
• A total of 314 patients were enrolled:
  • 197 diagnosed with post-ET MF
  • 117 diagnosed with post-PV MF
• Additionally, the survival of patients with primary MF collected during a nationwide survey between 2012 and 2015 was compared with this patient cohort

Results

Clinical characteristics

• Median age for both patient groups was 70 years
• The percentage of males in the post-ET group was 49.7% vs 53.8% in the post-PV group
• Median time to diagnosis for patients with post-ET was 9.6 years vs 10.4 years for patients with post-PV
  • There were no significant differences between these characteristics
• Across both patient cohorts, weight loss was the most frequently reported constitutional symptom
• Clinical characteristics identified as having a significant difference between the two patient cohorts are shown in Table 1

Table 1. Clinical characteristics that differ significantly between patients with post-ET and post-PV MF*

ET, essential thrombocythemia; Hb, hemoglobin; JAK2, Janus kinase 2; MF, myelofibrosis; PV, polycythemia vera; WBC, white blood cell. *Adapted from Shide et al.1
Characteristic, % (unless otherwise stated)	Post-ET MF (n = 197)	Post-PV MF (n = 117)	p value
Splenomegaly	68.9	81.2	0.024
Median WBC, ×109/L	8,820	14,400	<0.001
WBC >25, ×109/L	11.7	23.1	0.012
Median Hb, g/L	9.4	10.7	<0.001
Hb <10, g/dL	60.4	41.9	0.002
Median platelets, ×109/L	38.3	27.4	<0.001
JAK2V617F mutation	56.3	96.2	<0.001

All other clinical characteristics, including transfusion dependence, median lactate dehydrogenase levels, and circulating blasts ≥1%, showed no significant difference between the two patient cohorts

Treatment

• The median follow-up for all patients was 2.21 years
• Over this period, 92.3% of patients with post-ET MF received treatment vs 87.8% of patients with post-PV MF
• There was no difference in treatment choice between the two patient cohorts
• Ruxolitinib was the most commonly used treatment, followed by hydroxyurea
  • Overall, 74.6% of patients with post-ET MF received ruxolitinib vs 83.8% of patients with post-PV MF
• A total of 8.3% of patients received allogenic hematopoietic stem cell transplantation

Survival outcomes

• 3-year overall survival rates were similar between the two patient cohorts
  • Patients with post-ET MF had a 3-year overall survival rate of 0.742 vs 0.768 for patients with post-PV MF
• The combined 3-year overall survival of all patients with post-ET and post-PV MF vs patients with primary MF was 0.754 vs 0.626, respectively
• There was a total of 53 deaths in the post-ET patient group and 29 deaths in the post-PV group
  • Leukemic transformation was the leading cause of death

Conclusion

Differences in hematologic parameters and a higher frequency of splenomegaly in patients with post-PV MF were consistent with previous reports. The proportion of patients in both groups with constitutional symptoms was also similar. Limitations of the analysis include potential racial bias, due to the study being conducted in Japan, as well as a lack of data on the duration and dosage of ruxolitinib treatment. Overall, this prospective analysis provides valuable insight into real-world patient and prognostic data for these secondary diseases in the ruxolitinib treatment era.